Celselect Research Grant Program

Exciting research starts here with our 10 Celselect Research Grant recipients

We are pleased to announce the 10 researchers selected as Celselect Grant recipients! Selection was based upon a submitted application that included a 1-year research proposal that would utilize the Genesis Cell Isolation System and Celselect Slides™ in their research. Recipients were selected based on the feasibility of their proposed research, contribution of their research results to the greater scientific community, and the ability for adoption of research methodologies by other researchers in their discipline. These groundbreaking projects cover topics ranging from circulating tumor cells (CTCs) and cancer metastasis to exercise-induced conditioning of PBMCs to enhance vascular health. Below is the list of the Celselect Grant Recipients along with a summary of their proposed Grant research. Check back regularly for updates on their research, webinar presentations, conference talks, and scientific posters and publications.

• Sophia Abusamra, BS, Claire Edwards, PhD, and Alastair Lamb, MD PhD, University of Oxford

  Grant Research Title: Genomic interrogation of circulating disease in prostate cancer

  Prostate cancer diagnostics and prognostics are complicated by the shortcomings of existing histology and biomarkers to differentiate lethal from non-lethal disease. In our study, the genomics and metabolic plasticity of circulating tumor cells (CTCs) in prostate cancer will be investigated. Using the Genesis System with Celselect Slides™ circulating tumor cells (CTCs) in the blood and lymphatic fluid of men with high risk localized prostate cancer will be captured and recovered for ‘fingerprint’ analysis using scRNA-seq to determine the clone of origin in the primary tumor. Spatial transcriptomics will be used to identify histologically benign prostate regions containing genomic features of lethal disease. The presence of such cells in localized disease is little-studied and would signify a logical precursor event to demonstrable metastatic disease, while the presence of tumor cells in lymphatic fluid of patients with prostate cancer has not been previously studied. Finally, captured CTCs will be cultured using a novel microfluidic approach for optimal expansion of single cells for CTC functional analysis and metabolic profiling to give insights into the metabolic plasticity driving disease progression and/or response that could inform treatment decisions.

• Remi Klotz, PhD, University of Maryland School of Medicine

  Grant Research Title: Uncovering the molecular vulnerabilities of circulating tumor cells

  To date, no studies have definitively identified the underlying molecular mechanisms that allow tumor cells to penetrate blood vessel walls and enter circulation. Understanding the molecular mechanisms of intravasation is crucial for the development of therapeutic strategies to prevent metastasis. In our study, we will conduct a genome-wide CRISPR activation (CRISPRa) screen in a syngeneic mouse tumor model in combination with Genesis Cell Isolation System and Celselect Slides™ for the isolation of rare cells to uncover genetic determinants of cancer cell intravasation and survival in the bloodstream. Relative enrichment for sgRNA from isolated mouse CTCs derived from two mouse breast cancer cell lines transplanted in immunocompetent mice will be determined by comparing results to the transduced tumor cells before injection and corresponding primary tumor. Finally, to assess the clinical relevance of the top hits, protein expression analysis of these candidates in our established patient-derived CTC lines and CTCs freshly isolated from patients (10-20 patients) will be performed by direct immunolabeling on Celselect Slides™.

• Mohamed Omar, MD, Weill Cornell Medicine

  Grant Research Title: Deciphering PCa Bone Metastasis Mechanisms through Targeted CTC Isolation

  Prostate cancer (PCa) accounts for more than 10% of cancer-related deaths in men, which primarily results from bone metastasis. Gaining a comprehensive understanding of the molecular mechanisms driving bone metastasis is crucial for developing targeted therapies and improving risk prediction for patients with PCa. The aim of our research is to elucidate the molecular mechanisms driving PCa bone metastasis by isolating and characterizing CTCs from patients using the Genesis Cell Isolation System and Celselect Slides™. Subsequently, gene expression analysis will be performed on isolated CTCs to identify differentially expressed genes associated with bone metastasis. Our group is comprehensively characterizing the tumor microenvironment (TME) in genetically-engineered mouse models (GEMMs) of PCa using scRNA-seq and Visium spatial transcriptomics. Our goal is to identify molecular and spatial signatures associated with PCa progression from locally-advanced to metastatic disease which will be used to develop a robust multimodal predictive system for bone metastasis in PCa patients. Identification of CTC biomarkers will be crucial for enhancing the predictive performance of our system, which will assess the metastatic risk in PCa patients using the molecular and spatial profiles of their primary tumor biopsies and blood samples.

• Pamela Pinzani, PhD, University of Florence

  Grant Research Title: CTCs and cfDNA as immunotherapy response predictive biomarkers in NSCLC

  Our study is part of a clinical trial focused on detection of new predictive or prognostic biomarkers in non-small cell lung cancer (NSCLC) treated with immune check point inhibitors (ICI). We collect blood samples from enrolled patients before, during and after immunotherapy at different time points, to evaluate plasma cfDNA mutational status. Our study will combine cfDNA targeted-NGS analysis (already on going and funded) with CTCs evaluation for a cohort of patients with advanced NSCLC treated with PD-1 or PD-L1 inhibitors. For this purpose, blood samples from selected patients will be collected before therapy and during the follow-up period with plasma used for size-based cell capture of CTCs using the Genesis System with Celselect Slides™. Captured NSCLC CTCs will be identified by direct staining on Celselect Slides™ with a nuclear dye (DAPI), and fluorescent antibodies against surface biomarkers for lung cells (e.g. EGFR, CKs) and PD-L1 (ICI target) followed by microscopic enumeration and characterization. Additional sample aliquots may be processed for CTC cell enrichment and recovery for downstream molecular analyses. The goal of our research is to combine different circulating biomarkers (CTCs and cfDNA) that will identify a correlation with clinical outcome, enabling the identification of an immunotherapy predictive biomarker, potentially conferring a clinical utility to liquid biopsy in this scenario.

• Amanda Linkous, PhD, Vanderbilt University

  Grant Research Title: Brain organoids: Investigating the role of CTCs in SCLC and melanoma brain metastasis

  Despite targeted therapies and immunotherapies, metastatic disease remains the leading cause of death in cancer patients. Brain metastases in particular are very challenging to treat since surgical removal is often impossible without damaging vital regions of the brain. Though brain metastases have been reported in more than 50% of SCLC patients and more than 70% of metastatic melanoma patients, the mechanisms by which these tumor cells invade and adapt to the human brain microenvironment are still not well understood. We hypothesize that tumor cells form organ-site-specific robust tumor ecosystems via cellular plasticity. To test this hypothesis, we will isolate and expand CTCs from individual SCLC and melanoma patients using the Genesis System and Celselect Slides™ to a library of CTCs that can be shared with the greater SCLC and melanoma communities. Additionally, we will characterize molecular phenotypes of patient-derived CTCs captured with Celselect when grown in an hESC-derived organoid model of the brain that we developed to study the growth of SCLC and melanoma metastases. Our previous findings revealed that SCLC and melanoma cell lines successfully invade and form tumors within these “mini brains” within 24 hours of co-culture. Our results will determine whether the cerebral organoid microenvironment affects the cellular composition and gene expression profiles of CTCs from these patients.

• Esther Mettler, PhD, Johannes Gutenberg University of Mainz

  Grant Research Title: Karyotyping of CTCs in patients with neuroendocrine neoplasia

  The presence of CTCs is an independent prognostic factor associated with a significantly increased risk of death in patients with neuroendocrine neoplasia (NEN). Aneuploid quantification of CTCs serves as a valuable tool for assessing tumor progression, metastasis, and response to treatment. Currently, there is little information linking the success or failure of therapy, such as peptide receptor radionuclide therapy (PRRT) or tumor immunotherapy, to CTC karyotype in NEN patients. We are conducting the largest multicentre phase II study in high-grade NEN patients to evaluate the efficacy and safety of avelumab, an anti-PD-L1 immunotherapy, alone or in combination with cabozantinib in metastatic progressive neuroendocrine carcinoma (NEC G3). Our study aims to differentiate NEN patients based on CTC aneuploidy to tailor personalized treatment plans. This will help to identify patients who will benefit from checkpoint inhibitors with or without chemotherapy or PRRT and those who may not respond to treatment. We will use the Genesis System and Celselect Slides™ for CTC capture and fluorescent immunostaining for NEN markers. We will analyze aneuploidies of different chromosomes in enriched CTCs and statistically evaluate disease characteristics associated with CTC aneuploidy status. This research will guide more effective and personalized cancer therapy for NEN patients.

• Jose M. Moris M.S. and Yunsuk Koh, Ph.D, Baylor University

  Grant Research Title: Exercise-induced Hypercapnic Conditioning of PBMCs

  Peripheral blood mononuclear cells (PBMCs) are a subset of white blood cells whose differentiation lineage can be conditioned based upon the environment in which they are found. Exposure to hypoxia has become an agent of interest to polarize monocytes into anti-inflammatory macrophages and stimulate the expression of angiogenic and vascular remodeling peptides. Our laboratory is exploring the ability to extrapolate a hypoxic condition from a cell culture environment to human-induced conditioning by utilizing transient exposure to exercise-induced hypercapnia. Our aim is to isolate PBMCs pre- and post-transient exercise-induced hypercapnia in humans, followed by cell culture paired with continuous microscopic imaging. However, one challenge is to isolate macrophages from PBMCs that have been cultured without using a major downstream application such as flow cytometry. Using the Genesis System to capture and enumerate PBMCs, we will examine the ability of transient exercise-induced hypercapnia to condition PBMCs and provide in vivo benefits based upon their in vitro adaptation. Our goal is to develop a specific exercise method that can target the immune system and promote vascular adaptations by increasing the angiogenic stimulus provided by PBMCs.